Rat movements reflect internal decision dynamics in an evidence accumulation task.

Perceptual decision-making involves multiple cognitive processes, including accumulation of sensory evidence, planning, and executing a motor action. How these processes are intertwined is unclear; some models assume that decision-related processes precede motor execution, whereas others propose that movements reflecting ongoing decision processes occur before commitment to a choice. Here we combine two complementary methods to study the relationship between decision processes and the movements leading up to a choice.

A General, Noise-Driven Mechanism for the 1/f-Like Behavior of Neural Field Spectra.

Consistent observations across recording modalities, experiments, and neural systems find neural field spectra with 1/f-like scaling, eliciting many alternative theories to explain this universal phenomenon. We show that a general dynamical system with stochastic drive and minimal assumptions generates 1/f-like spectra consistent with the range of values observed in vivo without requiring a specific biological mechanism or collective critical behavior.

In vivo imaging in transgenic songbirds reveals superdiffusive neuron migration in the adult brain.

Neuron migration is a key phase of neurogenesis, critical for the assembly and function of neuronal circuits. In songbirds, this process continues throughout life, but how these newborn neurons disperse through the adult brain is unclear. We address this question using in vivo two-photon imaging in transgenic zebra finches that express GFP in young neurons and other cell types.

Rat movements reflect internal decision dynamics in an evidence accumulation task.

Perceptual decision-making involves multiple cognitive processes, including accumulation of sensory evidence, planning, and executing a motor action. How these processes are intertwined is unclear; some models assume that decision-related processes precede motor execution, whereas others propose that movements reflecting on-going decision processes occur before commitment to a choice. Here we develop and apply two complementary methods to study the relationship between decision processes and the movements leading up to a choice.

Decreased thalamocortical connectivity in resolved Rolandic epilepsy.

Objective: Median nerve somatosensory evoked fields (SEFs) conduction times reflect the integrity of neural transmission across the thalamocortical circuit. We hypothesized median nerve SEF conduction time would be abnormal in children with Rolandic epilepsy (RE).

Methods: 22 children with RE (10 active; 12 resolved) and 13 age-matched controls underwent structural and diffusion MRI and median nerve and visual stimulation during magnetoencephalography (MEG).

The 1/f-like behavior of neural field spectra are a natural consequence of noise driven brain dynamics.

Consistent observations across recording modalities, experiments, and neural systems find neural field spectra with 1/f-like scaling, eliciting many alternative theories to explain this universal phenomenon. We show that a general dynamical system with stochastic drive and minimal assumptions generates 1/f-like spectra consistent with the range of values observed , without requiring a specific biological mechanism or collective critical behavior.

Spike height improves prediction of future seizure risk.

Objective: We evaluated whether interictal epileptiform discharge (IED) rate and morphological characteristics predict seizure risk.

Methods: We evaluated 10 features from automatically detectable IEDs in a stereotyped population with self-limited epilepsy with centrotemporal spikes (SeLECTS). We tested whether the average value or the most extreme values from each feature predicted future seizure risk in cross-sectional and longitudinal models.

Assessing evidence accumulation and rule learning in humans with an online game.

Evidence accumulation, an essential component of perception and decision making, is frequently studied with psychophysical tasks involving noisy or ambiguous stimuli. In these tasks, participants typically receive verbal or written instructions that describe the strategy that should be used to guide decisions. Although convenient and effective, explicit instructions can influence learning and decision making strategies and can limit comparisons with animal models, in which behaviors are reinforced through feedback.

Alpha synuclein processing by MMP-3 - implications for synucleinopathies.

α-Synuclein (aSyn) is a protein implicated in physiological functions such as neurotransmitter release at the synapse and the regulation of gene expression in the nucleus. In addition, pathological aSyn assemblies are characteristic for a class of protein aggregation disorders referred to as synucleinopathies, where aSyn aggregates appear as Lewy bodies and Lewy neurites or as glial cytoplasmic inclusions. We recently discovered a novel post-translational pyroglutamate (pGlu) modification at Gln79 of N-truncated aSyn that promotes oligomer formation and neurotoxicity in human synucleinopathies.

IRE1-Mediated Unfolded Protein Response Promotes the Replication of Tick-Borne Flaviviruses in a Virus and Cell-Type Dependent Manner.

Tick-borne flaviviruses (TBFV) can cause severe neurological complications in humans, but differences in tissue tropism and pathogenicity have been described for individual virus strains. Viral protein synthesis leads to the induction of the unfolded protein response (UPR) within infected cells. The IRE1 pathway has been hypothesized to support flavivirus replication by increasing protein and lipid biogenesis.

Single-Target Versus Multi-Target Drugs Versus Combinations of Drugs With Multiple Targets: Preclinical and Clinical Evidence for the Treatment or Prevention of Epilepsy.

Rationally designed multi-target drugs (also termed multimodal drugs, network therapeutics, or designed multiple ligands) have emerged as an attractive drug discovery paradigm in the last 10-20 years, as potential therapeutic solutions for diseases of complex etiology and diseases with significant drug-resistance problems. Such agents that modulate multiple targets simultaneously are developed with the aim of enhancing efficacy or improving safety relative to drugs that address only a single target or to combinations of single-target drugs. Although this strategy has been proposed for epilepsy therapy >25 years ago, to my knowledge, only one antiseizure medication (ASM), padsevonil, has been intentionally developed as a single molecular entity that could target two different mechanisms.

Interplay between the genetics of personality traits, severe psychiatric disorders and COVID-19 host genetics in the susceptibility to SARS-CoV-2 infection.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, with its impact on our way of life, is affecting our experiences and mental health. Notably, individuals with mental disorders have been reported to have a higher risk of contracting SARS-CoV-2. Personality traits could represent an important determinant of preventative health behaviour and, therefore, the risk of contracting the virus.

Generation of Scale-Invariant Sequential Activity in Linear Recurrent Networks.

Sequential neural activity has been observed in many parts of the brain and has been proposed as a neural mechanism for memory. The natural world expresses temporal relationships at a wide range of scales. Because we cannot know the relevant scales a priori, it is desirable that memory, and thus the generated sequences, is scale invariant.

Ex vivo limb perfusion for traumatic amputation in military medicine.

Background: Limb loss has a drastic impact on a patient's life. Severe trauma to the extremities is common in current military conflicts. Among other aspects, "life before limb" damage control surgery hinders immediate replantation within the short post-traumatic timeframe, which is limited in part by the ischemic time for successful replantation.

Critical analysis of the value of the rabbit median nerve model for biomedical research on peripheral nerve grafts.

The rabbit has been proposed to represent an animal model that allows studying peripheral nerve regeneration across extended gap lengths. We describe here our experiences with the rabbit median nerve model and the obstacles it comes along with. This short communication is meant to inform the community and to prevent other researcher from investing time and animal lives in a model with low translational power.

A neural circuit model for a contextual association task inspired by recommender systems.

Behavioral data shows that humans and animals have the capacity to learn rules of associations applied to specific examples, and generalize these rules to a broad variety of contexts. This article focuses on neural circuit mechanisms to perform a context-dependent association task that requires linking sensory stimuli to behavioral responses and generalizing to multiple other symmetrical contexts. The model uses neural gating units that regulate the pattern of physiological connectivity within the circuit.

Reprogramming of DNA methylation at NEUROD2-bound sequences during cortical neuron differentiation.

The characteristics of DNA methylation changes that occur during neurogenesis in vivo remain unknown. We used whole-genome bisulfite sequencing to quantitate DNA cytosine modifications in differentiating neurons and their progenitors isolated from mouse brain at the peak of embryonic neurogenesis. Localized DNA hypomethylation was much more common than hypermethylation and often occurred at putative enhancers within genes that were upregulated in neurons and encoded proteins crucial for neuronal differentiation.

Attenuation of epileptogenesis by 2-deoxy-d-glucose is accompanied by increased cerebral glucose supply, microglial activation and reduced astrocytosis.

Rationale: Neuronal excitability and brain energy homeostasis are strongly interconnected and evidence suggests that both become altered during epileptogenesis. Pharmacologic modulation of cerebral glucose metabolism might therefore exert anti-epileptogenic effects. Here we provide mechanistic insights into effects of the glycolytic inhibitor 2-deoxy-d-glucose (2-DG) on experimental epileptogenesis by longitudinal 2-deoxy-2[F]fluoro-d-glucose positron emission tomography ([F]FDG PET) and histology.

Discovery and Preclinical Characterization of 5-[4,6-Bis({3-oxa-8-azabicyclo[3.2.1]octan-8-yl})-1,3,5-triazin-2-yl]-4-(difluoromethyl)pyridin-2-amine (PQR620), a Highly Potent and Selective mTORC1/2 Inhibitor for Cancer and Neurological Disorders.

Mechanistic target of rapamycin (mTOR) promotes cell proliferation, growth, and survival and is overactivated in many tumors and central nervous system disorders. PQR620 (3) is a novel, potent, selective, and brain penetrable inhibitor of mTORC1/2 kinase. PQR620 (3) showed excellent selectivity for mTOR over PI3K and protein kinases and efficiently prevented cancer cell growth in a 66 cancer cell line panel.

Introduction: Thematic Papers Issue on Peripheral Nerve Regeneration and Repair.

Injuries to the peripheral nerves result in loss of motor, sensory and autonomic functions in the denervated segments of the body, thus having strong impact in the quality of life of affected patients. Neurons are able to regenerate their injured axons in the peripheral nerves; however, the endogenous repair mechanisms usually do not allow for a satisfactory functional recovery, especially after severe nerve injuries. The interest on regeneration after peripheral nerve injuries has increased in the recent years due to the numerous advances derived from studies of neurobiology, cell therapy, and tissue engineering.

Blood-Brain Barrier Leakage during Early Epileptogenesis Is Associated with Rapid Remodeling of the Neurovascular Unit.

Increased permeability of the blood-brain barrier (BBB) following cerebral injury results in regional extravasation of plasma proteins and can critically contribute to the pathogenesis of epilepsy. Here, we comprehensively explore the spatiotemporal evolution of a main extravasation component, albumin, and illuminate associated responses of the neurovascular unit (NVU) contributing to early epileptogenic neuropathology. We applied translational MR imaging and complementary immunohistochemical analyses in the widely used rat pilocarpine post-status epilepticus (SE) model.

Semantic future thinking and executive functions at age 4: The moderating role of frontal brain electrical activity.

Previous studies provide conflicting results regarding the relation between future thinking and executive functioning during early childhood. Furthermore, little is known of the neural mechanisms involved in future thinking during early childhood. We examined the moderating role of frontal electroencephalogram (EEG) activity on the relation between executive functioning and semantic future thinking performance in a sample of 4-year-old children.